2017 Fiscal Year Final Research Report
Generation of chimeric antigen receptors with different reactivity for a tumor antigen
| Project/Area Number |
16H07025
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Ehime University |
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Principal Investigator |
Ochi Toshiki 愛媛大学, 医学系研究科, 講師 (10571086)
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Keywords | キメラ抗原受容体 / 一本鎖抗体 / NY-ESO-1 |
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| Outline of Final Research Achievements |
Modified antibodies which activate immune cells with cancer specificity has been developed, thereby cancer immunotherapy has shown great success. In this study, we focused on optimizing single chain fragment variables (scFvs) for further development of antibody-based immunotherapy. Using chimeric antigen receptor T cells (CAR-T cells) and an HLA-A2/NY-ESO-1 complex expressed by tumor cells as models, we have established a new scFv generation system which can fine-tune the reactivity of CAR-T cells. Newly generated scFv-expressing CAR-T cells showed target-specific reactivity with different degrees. Among them, we have successfully identified scFv-optimized CAR-T cells which show sufficient antitumor reactivity with minimal unwanted cross-reactivity. This system allows us to optimize each scFv for each antibody-based modality, resulting in the advancement of successful cancer immunotherapy utilizing modified antibodies.
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| Free Research Field |
血液内科学、腫瘍免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
我々が確立した新規技術を用いれば、scFv内の可変領域配列を自由に変化させることで、scFvの標的認識様式を繊細に調律することが可能となる。そして、CAR-T細胞の抗がん活性を指標としながら新規scFvを作製・同定することが可能となる。本技術を応用すれば、様々な抗体製剤の治療効果に主眼においたこれまでにはない迅速かつ網羅的な抗体医薬品作製が可能となるため、がんを含めた難治性疾患に対する免疫療法製剤開発の領域におけるインパクトは大きく、社会的意義も高いと考えられる。
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